The objective of this research plan is to develop a high resolution genetic linkage map of human chromosome 9. Such maps will facilitate the identification and localization of human disease genes. Furthermore, genetic maps are a prerequisite for accurate carrier detection and prenatal diagnosis of hereditary disorders. The first aim of this research is to identify highly polymorphic simple sequence repeat markers that span the length of chromosome 9. This will be accomplished by screening a cosmid library for repeat sequences, subcloning positive cosmids, and sequencing to identify PCR primers. Subsequently, the CEPH reference pedigrees will be genotyped using these markers and a genetic linkage map constructed using the computer programs LINKAGE and CRIMAP. If existing chromosome 9 probes are found to occupy critical regions in the linkage map, the inserts will be screened for repeats and sequenced to facilitate PCR genotyping. Sequence tagged sites (STSs) will be identified for all probes in order to facilitate comparison of the genetic and physical maps. Ultimately, a genetic linkage map of human chromosome 9 constructed using markers identified by STSs will lead to the physical localization and cloning of many human disease genes: including those for tuberous sclerosis, Friedreich's ataxia, and torsion dystonia.